Monday, January 15, 2007

Stem Cells Create Beating Heart Muscle

Although it is too early to tell how this might be incorporated into an actual human heart, the implications of this work for heart failure patients are staggering:

The researchers, whose study appears in the on-line edition of the prestigious journal Circulation Research, created the heart tissue in their lab by sorting human embryonic stem cells that turned into heart muscle cells and growing them together with endothelial cells and embryonic fibroplasts. The culture was carried out in three dimensions on a scaffold made of self-destructing sponge material that the researchers also created in their lab. In the future, they will look into the possibility of implanting the engineered cardiac tissue, with the blood vessels improving the implantation of the new tissue and its connection to the blood system.

The technique is aimed eventually at helping patients who have cardiac insufficiency due to heart attacks.

Not only are beating cells produced, but the blood supply to nurture them. The cells used were "pluripotent human embryonic stem cells of the H9.2 clone (passage 30-60) that were grown in the undifferentiated state on top of mouse embryonic fibroblast feeder layer."

Prestigious? Check the impact factor. Circulation Research is a third tier journal at best. If this was really novel ES cell work, it would have been in Cell, Science, or Nature, not some backwards clinical journal.

Synchronously beating cells are a common occurence in ES cell culture; it's not clear that these cells are anything special.

I'd suspect that this is probably meant to bolster the patent application for the sponge matrix they invented. Israel aggressively promotes research that could lead to patentable inventions.

However -- could you point me to the article in question at Circulation Research? I can't follow the direct pointer you provide (as I don't have a subscription to login to), and then when I try to search for it (here, whether using the doi or, say, "pluripotent") the article doesn't seem to turn up.

The supplemental methods are also freely available. It's fairly clear from the methods section that they didn't do an experiment that would demonstrate that this was functionally equivalent to real cardiac muscle.

Alas,the PDF requires payment for download unless you have a subscription.

And while no doubt this is not a breakthrough development (it's important I think to emphasize that stem cell research is still in the basic, not applied, research stage — meaning patient treatments aren't imminent — California's Institute for Regenerative Medicine just launched with $3 billion in taxpayer funding, for instance, hopes to have “preliminary evidence of clinical efficacy” for one patient treatment for some disease by a decade from now), still just in terms of exhibition of basic capability as an indicator for the future, this seems a significant step.

It's not even close to a breakthrough, Most of the leading scientists in the field can't even culture ES cells correctly, let alone control their differentiation. Stem cell therapies are 10 years away in the same sense that fusion power is 10 years away, that is, only in the arguments of those applying for government grants.

I don't think these scientists were trying to patent the therapy, but the potential use of their gel/sponge/matrix/whatever for 3D culture. Definitely patentable. It would have been less of a stunt if they had used breast cancer cells to grow a vascularized 3D culture of milk-duct-like tissue, but you can already do that with matrigel, so it would lack novelty.

James: I said it wasn't a “breakthrough” — are you denying that it's a “significant step”? How about just a step?

I think your pessimism — except with regard to the fact that it's going to take many more years (a decade or two in my view) to attain real fluency in wielding this technology — is misplaced, particularly the comparison with fusion. Not only is fusion (finally) inching towards success as a technology (and it's been a very difficult problem), but it is a totally new technology of which nobody knew in advance whether it would or how to make it work, and it's been a long, painstaking process of ironing out the problems in controlling a electrically-active plasma gas (which continually tries to whip out of control) via magnetic and electric fields. But as I say, that long project now appears to be approaching success.

Stem cell technology is entirely different. Rather than having to invent stem cells or something like them whole cloth out of nothing in order to accomplish cellular regeneration, we can and are simply copying for the most part the high technology that we see exhibited all around us in the biosphere. It's clear that the technology can and does work, we simply need to find out (copy) how it does it.

And a portion of how it works, it seems pretty clear, is that stem cells — especially embryonic stem cells, which are most general in their capabilities (possessing the ability to grow into any tissue in the human body) — require regulation to properly function and grow smoothly and under control into the needed cell types and tissues; while most of the experimentation that's been done with stem cells to date (best I can tell) involves things like injecting stem cells into an animal or human patient totally without regulation. As a result, sometimes you get beneficial results, while in other circumstances you get masses of uncontrolled differentiating cells — a teratoma, or kind of cancer.

To my mind, this is much like launching a series of rockets totally lacking in a guidance system and being surprised when they oftentimes or always crash. Build a rocket with proper guidance and it won't crash.

Thus, we need to learn much better how embryo and adult organisms keep their stem cells regulated and under control. Once again, this isn't so much a matter of invention (since the technology already exists out in the world) as that of observation, copying, and improvement to what is seen.

Anonymous: You could be right, or wrong, we just don't know. As the recent research report which announced the amniotic fluid stem cell results notes, it's not clear yet whether the AF stem cells truly are pluripotent — able to grow into all the cells and tissues of the body. Since as noted before, we're still in the basic research stage and will be for many years, it's way too early (if ever) to foreclose study of any aspect of the body's regenerative system, from embryo through adult, as it's the system of how stem cells work (including how it's properly regulated) that we need to learn about. In the meantime, if any promising treatments turn up, involving say AF or adult stem cells, then we can make use of those.

With regard to embryonic stem cells, it's worth noting a couple of things. First, embryos per se need not and would not be required for procuring embryonic stem cells for such treatments; as once a few such cells have been initially “teased” from an embryo to form a self-sustaining, self-reproducing “line” of embryonic stem cells for research (assuming it's a high-quality line, not contaminated by animal genes and potentially viruses as I understand a number of the existing lines are subject to), then there's no need to go back to embryos for more cells to use in research or treatments.

Secondly, once we understand how embryonic stem cells do what they do, it's highly likely that there will be no need to use embryonic stem cells (even coming from an immortal line of such cells) in patient treatments — which would inevitably (since the embryonic cells come from a different individual having different DNA) be subject to rejection issues — at all. Instead, we will learn how to transform the patient's own body cells into the equivalent of embryonic stem cells to serve in his own treatment. Much progress has already been made in this area, as this report from the journal Nature delves into in detail.

That is interesting. With the ability to create beating heart muscles, we'll be able to heal people that have heart disease but the thing I am not looking forward to is the price of this technology. Since this will be approved in the next 10 years, probably six, the price will only be affordable by millionaires and not for the common folk like every other medicine. I hope that this becomes affordable by most of the public in 20 years but more than likely it won't.

You needn't worry that you won't be able to afford the treatment in 6, 10, or 20 years. It simply won't exist. All the ES cell lines, including the "non-presidential" ones generated at Doug Melton's lab over at Harvard, are miserable failures at growing for many passages. Like I said before, people don't even know how to culture them long enough to do valuable research on them.

About Me

Westby G. Fisher, MD, FACC is a board certified internist, cardiologist, and cardiac electrophysiologist (doctor specializing in heart rhythm disorders) practicing at NorthShore University HealthSystem in Evanston, IL, USA and is a Clinical Associate Professor of Medicine at University of Chicago's Pritzker School of Medicine. He entered the blog-o-sphere in November, 2005.
DISCLAIMER: The opinions expressed in this blog are strictly the those of the author(s) and should not be construed as the opinion(s) or policy(ies) of NorthShore University HealthSystem, nor recommendations for your care or anyone else's. Please seek professional guidance instead.